Jorge Garcia Borrega1,2, Katrin Heindel1,2, Yasemin Göreci3, Clemens Warnke3, Oezguer A Onur3, Matthias Kochanek1,2, Natalie Schub4, Francis Ayuk5, Dominic Wichmann6, Boris Böll7,8. 1. Klinik I für Innere Medizin, Hämatologie-Onkologie und Internistische Intensivmedizin, Klinikum der Universität Köln, Kerpener Str. 62, 50937, Köln, Deutschland. 2. Klinik I für Innere Medizin, Centrum für Integrierte Onkologie Aachen Bonn Köln Düsseldorf (CIO ABCD), Klinikum der Universität zu Köln, Köln, Deutschland. 3. Klinik für Neurologie, Universitätsklinikum Köln, Köln, Deutschland. 4. Medizinische Klinik II, Universitätsklinik Schleswig-Holstein, Campus Kiel, Kiel, Deutschland. 5. Interdisziplinäre Klinik und Poliklinik für Stammzelltransplantation, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland. 6. Zentrum für Anästhesiologie und Intensivmedizin, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland. 7. Klinik I für Innere Medizin, Hämatologie-Onkologie und Internistische Intensivmedizin, Klinikum der Universität Köln, Kerpener Str. 62, 50937, Köln, Deutschland. boris.boell@uk-koeln.de. 8. Klinik I für Innere Medizin, Centrum für Integrierte Onkologie Aachen Bonn Köln Düsseldorf (CIO ABCD), Klinikum der Universität zu Köln, Köln, Deutschland. boris.boell@uk-koeln.de.
Abstract
BACKGROUND: The transfusion of chimeric antigen receptor (CAR) T‑cells has become established as a new treatment option in oncology; however, this is regularly associated with immune-mediated side effects, which can also run a severe course and necessitate a specific treatment and intensive medical treatment. MATERIAL AND METHODS: A literature review was carried out on CAR T-cell therapy, toxicities and the management of side effects. RESULTS: The cytokine release syndrome (CRS) and the immune effector cell-associated neurotoxicity syndrome (ICANS) regularly occur shortly after CAR T-cell treatment. The symptoms of CRS can range from mild flu-like symptoms to multiorgan failure. In addition to mild symptoms, such as disorientation and aphasia, ICANS can also lead to convulsive seizures and brain edema. The management of CRS and ICANS is based on the severity according to the grading of the American Society for Transplantation and Cellular Therapy (ASTCT). Tocilizumab and corticosteroids are recommended for CRS and corticosteroids are used for ICANS. In the further course persisting hypogammaglobulinemia and cytopenia are frequent even months after the initial treatment and promote infections even months after CAR T‑cell therapy. DISCUSSION: Potentially severe complications regularly occur after CAR T-cell therapy. An interdisciplinary cooperation between intensive care physicians, hematologists, neurologists and specialists in other disciplines is of decisive importance for the optimal care of patients after CAR T‑cell therapy.
BACKGROUND: The transfusion of chimeric antigen receptor (CAR) T‑cells has become established as a new treatment option in oncology; however, this is regularly associated with immune-mediated side effects, which can also run a severe course and necessitate a specific treatment and intensive medical treatment. MATERIAL AND METHODS: A literature review was carried out on CAR T-cell therapy, toxicities and the management of side effects. RESULTS: The cytokine release syndrome (CRS) and the immune effector cell-associated neurotoxicity syndrome (ICANS) regularly occur shortly after CAR T-cell treatment. The symptoms of CRS can range from mild flu-like symptoms to multiorgan failure. In addition to mild symptoms, such as disorientation and aphasia, ICANS can also lead to convulsive seizures and brain edema. The management of CRS and ICANS is based on the severity according to the grading of the American Society for Transplantation and Cellular Therapy (ASTCT). Tocilizumab and corticosteroids are recommended for CRS and corticosteroids are used for ICANS. In the further course persisting hypogammaglobulinemia and cytopenia are frequent even months after the initial treatment and promote infections even months after CAR T‑cell therapy. DISCUSSION: Potentially severe complications regularly occur after CAR T-cell therapy. An interdisciplinary cooperation between intensive care physicians, hematologists, neurologists and specialists in other disciplines is of decisive importance for the optimal care of patients after CAR T‑cell therapy.
Authors: Stephen J Schuster; Michael R Bishop; Constantine S Tam; Edmund K Waller; Peter Borchmann; Joseph P McGuirk; Ulrich Jäger; Samantha Jaglowski; Charalambos Andreadis; Jason R Westin; Isabelle Fleury; Veronika Bachanova; S Ronan Foley; P Joy Ho; Stephan Mielke; John M Magenau; Harald Holte; Serafino Pantano; Lida B Pacaud; Rakesh Awasthi; Jufen Chu; Özlem Anak; Gilles Salles; Richard T Maziarz Journal: N Engl J Med Date: 2018-12-01 Impact factor: 91.245
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Authors: Daniel W Lee; Rebecca Gardner; David L Porter; Chrystal U Louis; Nabil Ahmed; Michael Jensen; Stephan A Grupp; Crystal L Mackall Journal: Blood Date: 2014-05-29 Impact factor: 22.113
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